Refinement Database

Database on Refinement of Housing, Husbandry, Care, and Use of Animals in Research

This database, created in 2000, is updated every four months with newly published scientific articles, books, and other publications related to improving or safeguarding the welfare of animals used in research.

Tips for using the database:

  • This landing page displays all of the publications in the database.
  • Use the drop-down menus to filter these publications by Animal Type, Setting, and/or Topic.
  • Clicking on a parent category (e.g., Rodent) will include publications relating to all the items in that category (e.g., Chinchilla, Gerbil, Guinea Pig, etc.).
  • You may also add a keyword to further narrow your search.
  • Please note that at this time, only publications dated 2010 or later (with some exceptions) can be filtered by Animal Type and Topic, and only publications dated 2020 or later (with some exceptions) can be filtered by Setting. Most publications older than 2010 can only be searched by keyword. 
Bozzay, J. D., Walker, P. F., Atwood, R. E. et al. 2023. Development, refinement, and characterization of a nonhuman primate critical care environment. PLOS ONE 18(3), e0281548.

Systemic inflammatory response remains a poorly understood cause of morbidity and mortality after traumatic injury. Recent nonhuman primate (NHP) trauma models have been used to characterize the systemic response to trauma, but none have incorporated...

Digranes, N., Haga, H. A., Nordgreen, J. 2023. High and hyper: Fentanyl induces psychomotor side-effects in healthy pigs. Animals 13(10), 1671.

Analgesic effects of fentanyl have been investigated using behavior. The behavioral effects of fentanyl and possible serotonergic influence are largely unknown. We therefore investigated behavioral effects of fentanyl, with or without the serotonin antagonist ketanserin...

Farag, A., Mandour, A. S., Hendawy, H. et al. 2023. A review on experimental surgical models and anesthetic protocols of heart failure in rats. Frontiers in Veterinary Science 10, 1103229.

Heart failure (HF) is a serious health and economic burden worldwide, and its prevalence is continuously increasing. Current medications effectively moderate the progression of symptoms, and there is a need for novel preventative and reparative...

Malik, A., Zavadil, J. A., Geusz, M. E. 2023. Using bioluminescence to image gene expression and spontaneous behavior in freely moving mice. PLOS ONE 18(1), e0279875.

Bioluminescence imaging (BLI) of gene expression in live animals is a powerful method for monitoring development, tumor growth, infections, healing, and other progressive, long-term biological processes. BLI remains an effective approach for reducing the number...

Mauthe von Degerfeld, M., Serpieri, M., Bonaffini, G. et al. 2023. Intranasal atomization of ketamine, medetomidine and butorphanol in pet rabbits using a mucosal atomization device. Animals 13(13), 2076.

A non-invasive method of drug delivery, intranasal atomization, has shown positive results in human medicine and in some animal species. The objective of this study was to evaluate the effects of intranasal atomization, compared to...

Miller, R., Grott, A., Patzkéwitsch, D. et al. 2023. Behavior of piglets in an observation arena before and after castration with local anesthesia. Animals 13(3), 529.

Surgical castration of piglets is generally recognized as a painful procedure, but there is currently no gold standard for the assessment of pain behavior in piglets. However, pain assessment is essential for evaluating the effectiveness...

Mirra, A., Maidanskaia, E. G., Carmo, L. P. et al. 2023. How is depth of anaesthesia assessed in experimental pigs? A scoping review. PLOS ONE 18(3), e0283511.

Despite the large number of pigs involved in translational studies, no gold standard depth of anaesthesia indicators are available. We undertook a scoping review to investigate and summarize the evidence that sustains or contradicts the...

Palumbo, G., Kunze, L. H., Oos, R. et al. 2023. Longitudinal studies on Alzheimer disease mouse models with multiple tracer PET/CT: Application of reduction and refinement principles in daily practice to safeguard animal welfare during progressive aging. Animals 13(11), 1812.

Longitudinal studies on mouse models related to Alzheimer disease (AD) pathology play an important role in the investigation of therapeutic targets to help pharmaceutical research in the development of new drugs and in the attempt...

Ruvira, S., Rodríguez-Rodríguez, P., Cañas, S. et al. 2023. Evaluation of parameters which influence voluntary ingestion of supplements in rats. Animals 13(11), 1827.

Drug safety and efficacy studies frequently use oral gavage, but repetitive usage may cause problems. Administration through voluntary ingestion represents an opportunity for refinement. We aimed to develop a protocol for voluntary ingestion of gelatin-based...

Wolter, A., Bucher, C. H., Kurmies, S. et al. 2023. A buprenorphine depot formulation provides effective sustained post-surgical analgesia for 72 h in mouse femoral fracture models. Scientific Reports 13(1), 3824.

Adequate pain management is essential for ethical and scientific reasons in animal experiments and should completely cover the period of expected pain without the need for frequent re-application. However, current depot formulations of Buprenorphine are...

Lupfer, G., Brandenburger, A., Machado, M. et al. 2023. Ultrasonic vocalizations near 30 kHz may indicate excitement rather than distress in female Wistar rats. Applied Animal Behaviour Science 261, 105881.

Rats emit ultrasonic vocalizations (USVs), sometimes referred to as 50-kHz vocalizations, during activities such as play and lower-frequency USVs, sometimes referred to as 22-kHz vocalizations, when experiencing distress. Definitions of 22-kHz vocalizations vary in terms...

Attokaren, M. K., Jeong, N., Blanpain, L. et al. 2023. BrainWAVE: A flexible method for noninvasive stimulation of brain rhythms across species. ENeuro 10(2) ENEURO.0257-22.2022.

Rhythmic neural activity, which coordinates brain regions and neurons to achieve multiple brain functions, is impaired in many diseases. Despite the therapeutic potential of driving brain rhythms, methods to noninvasively target deep brain regions are...

Broadfoot, C. K., Lenell, C., Kelm-Nelson, C. A. et al. 2023. Effects of social isolation on 50-kHz ultrasonic vocalizations, affective state, cognition, and neurotransmitter concentrations in the ventral tegmental and locus coeruleus of adult rats. Behavioural Brain Research 437, 114157.

Vocal communication, cognition, and affective state are key features of sustained health and wellness, and because vocalizations are often socially-motivated, social experience likely plays a role in these behaviors. The monoaminergic systems of the ventral...

Chakravarty, S., Donoghue, J., Waite, A. S. et al. 2023. Closed-loop control of anesthetic state in nonhuman primates. PNAS Nexus 2(10), 293.

Research in human volunteers and surgical patients has shown that unconsciousness under general anesthesia can be reliably tracked using real-time electroencephalogram processing. Hence, a closed-loop anesthesia delivery (CLAD) system that maintains precisely specified levels of...

Costa, G. L., Spadola, F., Di Pietro, S. et al. 2023. Tramadol vs. Lidocaine administered intraperitoneally and in incisional lines for the intraoperative and postoperative pain management of romifidine-telazol-anesthetized swine undergoing umbilical hernia repair. Animals 13(18), 2905.

The aim of the study was to compare the analgesic efficacy of tramadol and lidocaine for local anesthesia during umbilical hernia repair in swine. The study was performed on 66 large white crossbred swine. The...

Costea, R., Ene, I., Pavel, R. 2023. Pig sedation and anesthesia for medical research. Animals 13(24), 3807.

In clinical veterinary practice, proper training and expertise in anesthesia administration and monitoring are essential. Pigs are suitable experimental animals for many surgical techniques because they are similar in size to humans and have a...

Mirra, A., Hight, D., Kovacevic, A. et al. 2023. Sedline® miscalculation of depth of anaesthesia variables in two pigs due to electrocardiographic signal contamination. Animals 13(17), 2699.

Two young (11-week-old) pigs underwent sole propofol anaesthesia as part of an experimental study. The depth of anaesthesia was evaluated both clinically and using the electroencephalography(EEG)-based monitor Sedline; in particular, the patient state index, suppression...

Olczak, K., Penar, W., Nowicki, J. et al. 2023. The role of sound in livestock farming—Selected aspects. Animals 13(14), 2307.

To ensure the optimal living conditions of farm animals, it is essential to understand how their senses work and the way in which they perceive their environment. Most animals have a different hearing range compared...

Trujanovic, R., Rohrbach, H. 2023. Ultrasound-guided block of the sciatic and the femoral nerves in rabbits—A descriptive anatomical study. Animals 13(14), 2393.

The rabbit is a popular animal model for human biomechanical research involving surgery on the hind limb. Mortality is higher in rabbits when undergoing general anesthesia compared to dogs and cats. Moreover, due to their...

Krall, C., Hopper, L. M., Hutchinson, E. K. 2023. Mice just want to have fun: Playpens facilitate faster training in non-invasive techniques for improved refinement and well-being. Laboratory Animal Science Professional 11(4) (July/August), 22-24.

Practical mechanisms that can be implemented by animal facilities to enhance refinement include the use of non-aversive handling, non-invasive alternative procedures, and additional environmental enrichment. Thus, we sought to collate these techniques by developing a...

Benato, L., Murrell, J., Rooney, N. 2023. Determining a cut-off point for intervention analgesia in rabbits using the Bristol Rabbit Pain Scale. Veterinary Record 193(5), e2995.

Background: The objective of this study was to determine the threshold of the Bristol Rabbit Pain Scale (BRPS) indicating the need for intervention analgesia. Methods: Fourteen members of veterinary staff were recruited to rate rabbits...

Brake, M. E., Russ, B. P., Gansebom, S. et al. 2023. Effects of extended-release buprenorphine on mouse models of influenza. Comparative Medicine 73(6), 466–473.

Mice are widely used as small animal models for influenza infection and immunization studies because of their susceptibility to many strains of influenza, obvious clinical signs of infection, and ease of handling. Analgesia is rarely...

Buhr, P., Kolstrup, S., Nikolajsen, L.-L. et al. 2023. The anaesthetic effects of ketamine/xylazine/midazolam in C57Bl/6JRj mice. Scandinavian Journal of Laboratory Animal Science 49, 21–27.

We wished to improve the efficacy and safety of ketamine/xylazine anaesthesia in C57Bl/6JRj mice and achieve a surgical anaesthesia lasting 20-30 minutes, aiming at fewer anaesthesia related deaths and using the subcutaneous injection route to...

Costa, R. S., Ciotti-McClallen, M., Tilley, R. et al. 2023. Intramuscular alfaxalone with or without buprenorphine or hydromorphone provides sedation with minimal adverse effects in healthy rabbits (Oryctolagus cuniculus) in a randomized blinded controlled trial. Journal of the American Veterinary Medical Association 261(2), 223–228.

OBJECTIVE To evaluate the effects of alfaxalone administered IM with or without buprenorphine or hydromorphone in healthy rabbits (Oryctolagus cuniculus). ANIMALS 24 male rabbits undergoing elective orchiectomy between August 21, 2021, and November 6, 2021...

Lopez-Echeverria, G., Alamaw, E., Gorman, G. et al. 2023. Comparing three formulations of buprenorphine in an incisional pain model in mice. JAALAS 62(6), 531–537.

This study compared the therapeutic effects in mice of 3 different formulations of buprenorphine. These formulations were standard buprenorphine hydrochloride (Bup-HCL) and 2 different extended-release buprenorphine formulations (Bup-ER and Ethiqa-XR [Bup-XR]). Drugs were evaluated based...